Paramyxoviruses SV5 and HPIV2 assemble STAT protein ubiquitin ligase complexes from cellular components
Paramyxoviruses SV5 and HPIV2 assemble STAT protein ubiquitin ligase complexes from cellular components
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DOI：
10.1006/viro.2002.1773
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发表时间：
2002-12-20
期刊：
影响因子：
3.7
通讯作者：
Horvath, CM
中科院分区：
文献类型：
--
作者：
Ulane, CM;Horvath, CM
信号转导子和转录激活子（STAT）蛋白通常是长寿命的，但某些副粘病毒感染导致IFN应答性STAT 1或STAT 2的有效丧失。病毒编码的称为“V”的蛋白质的表达足以介导STAT蛋白质的破坏。STAT降解被蛋白酶体抑制剂阻断，强烈暗示泛素（Ub）-蛋白酶体靶向系统。我们证明了来自猿猴病毒5（SV 5）和II型人副流感病毒（HPIV 2）的V蛋白的细胞表达诱导STAT 1和STAT 2靶标的多泛素化。在体外，V蛋白在ATIP依赖性过程中催化Ub转移，该过程需要Ub激活（E1）和Ub缀合（E2）活性。此外，通过亲和纯化从人细胞中分离SV 5和HPIV 2 V相互作用蛋白伴侣，并揭示相关细胞蛋白的复合物。这种复合物包括STAT 1和STAT 2，以及受损的DNA结合蛋白DDB 1。此外，与细胞Ub连接酶复合物亚基家族相关的蛋白质cullin 4A（Cul 4A）与V蛋白相关。使用小干扰RNA分析DDB 1和Cul 4A在SV 5感染引起的STAT 1降解中的作用。这些发现证明了包括STAT 1、STAT 2、DDB 1和Cul 4A的V依赖性降解复合物的组装。与SCF型细胞E3酶的先前命名一致，我们将这种复合物称为VDC。(C)2002 Elsevier Science（美国）。
Signal transducer and activator of transcription (STAT) proteins are normally long-lived, but infection with certain Paramyxoviruses results in efficient loss of IFN-responsive STAT1 or STAT2. Expression of a virus-encoded protein called "V" is sufficient to mediate the destruction of STAT proteins. STAT degradation is blocked by proteasome inhibitors, strongly implicating the ubiquitin (Ub)-proteasome targeting system. We demonstrate that cellular expression of V proteins from simian virus 5 (SV5) and type II human parainfluenza virus (HPIV2) induces polyubiquitylation of STAT1 and STAT2 targets. In vitro, the V proteins catalyze Ub transfer in an ATIP-dependent process that requires both Ub-activating (E1) and Ub-conjugating (E2) activities. Furthermore, SV5 and HPIV2 V-interacting protein partners were isolated by affinity purification from human cells and reveal a complex of associated cellular proteins. This complex includes both STAT1 and STAT2, and the damaged DNA binding protein, DDB1. In addition, a protein related to a family of cellular Ub ligase complex subunits, cullin 4A (Cul4A), associated with the V proteins. The roles of both DDB1 and Cul4A in STAT1 degradation by SV5 infection were analyzed using small interfering RNAs. These findings demonstrate the assembly of a V-dependent degradation complex that includes STAT1, STAT2, DDB1, and Cul4A. In agreement with prior nomenclature on SCF-type cellular E3 enzymes, we refer to this complex as VDC. (C) 2002 Elsevier Science (USA).